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OBJECTIVE - To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.
RESEARCH DESIGN AND METHODS - We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.
RESULTS - In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90-1.16] per unit log-leptin increase) or women (1.05 [0.91-1.20]) but was associated with risk of diabetes in men (2.75 [2.14-3.52]) and women (1.54 [1.22-1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30-2.63]) but not in women (0.89 [0.64-1.26]).
CONCLUSIONS - Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.
Diabetes Care 32:308-310, 2009
Leptin is a pleiotropic adipokine, and circulating levels correlate with markers of body fat mass (1). Obesity is a known risk factor for the development of both cardiovascular disease (CVD) and type 2 diabetes, and leptin is a candidate mediator of these increased risks. Hyperleptinemia may promote atherosclerosis (2), and dysregulation of leptin signaling in obese individuals results in reduced fatty acid oxidation and glucose uptake (3).
There is evidence for (4-6) and against (7-10) leptin being a prospective risk marker for CVD, whereas there is evidence that leptin predicts diabetes risk independently of other confounders only in men (11-13). We aimed to clarify these risk associations by simultaneous comparison of end points in both sexes individually in a single study.
RESEARCH DESIGN AND METHODS - Methods of the PROspective Study of Pravastatin in the Elderly at Risk trial (PROSPER) as an ancillary risk association study have been reported (14). Between 1997 and 1999, 5,804 men and women aged 70-82 years were recruited from Scotland, Ireland, or the Netherlands if they had either preexisting vascular disease (coronary, cerebral, or peripheral) or increased risk of such disease because of risk factors. The institutional ethics review boards of all centers approved the protocol, and all participants gave written informed consent. The primary outcome was definite...